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(Circulation. 2004;109:1036-1040.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Reoxygenation of Hypoxic Coronary Smooth Muscle Cells Amplifies Growth-Retarding Effects of Ionizing Irradiation

Amina Arab, MD; Thorsten Grumann, MD; Roland Guttenberger, MD; Christoph Bode, MD; Christoph Hehrlein, MD

From the Departments of Cardiology (A.A., T.G., C.B., C.H.) and Radiotherapy (R.G.), University of Freiburg, Germany.

Correspondence to Christoph Hehrlein, MD, Professor of Medicine, Department of Cardiology, University Hospital, Freiburg Hugstetterstr. 55 79106, Freiburg i. Br., Germany. E-mail hehrlein{at}med1.ukl.uni-freiburg.de

Received July 11, 2003; de novo received September 3, 2003; revision received October 17, 2003; accepted October 28, 2003.

Background— Hypoxic human coronary smooth muscle cells (HCSMCs) are possible targets for brachytherapy to prevent restenosis after percutaneous transluminal coronary angiography. It is unclear whether growth kinetics and gene expression of these cells undergoing -irradiation are changed by reoxygenation.

Methods and Results— Hypoxic (H) and hypoxia-reoxygenated (H-R) HCSMCs were irradiated with -radiation at single doses of 4, 8, and 16 Gy using a ⁶⁰Co-source. Vascular endothelial growth factor gene expression of HCSMCs was dramatically suppressed in H-R versus H cells independent of the radiation dose (15±7% versus 2183±2023%, P<0.01, H-R versus H cells). An oxygen enhancement ratio of 1.8 was calculated after irradiation from the retarded growth of H-R versus hypoxic HCSMCs. Production of reactive oxygen species by HCSMCs after irradiation increased by 15±2% in H-R cells versus 7±1% in H cells (P<0.05).

Conclusions— Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of ionizing irradiation. On the basis of these findings, oxygenating radiosensitizers should be analyzed with regard to suitability for coronary brachytherapy to prevent restenosis.

Key Words: hypoxia • muscle, smooth • restenosis